In the open-label trial, 931 patients with disease progression after platinum-based therapy from 198 sites primarily in Europe, North America, and the Asia-Pacific region were randomized between January 2015 and February 2016 to receive atezolizumab at 1,200 mg every 3 weeks (n = 467) or physician’s choice of chemotherapy (n = 464). Chemotherapy consisted of vinflunine at 320 mg/m2 (55% of patients), paclitaxel at 175 mg/m2 (33%), or docetaxel at 75 mg/m2 (12%) every 3 weeks.

Randomization was stratified by PD-L1 expression (expression on < 1% [IC0] or 1% to < 5% [IC1] of tumor-infiltrating immune cells vs ≥ 5% of tumor-infiltrating immune cells [IC2/3]), chemotherapy type, liver metastases, and number of prognostic factors. The primary endpoint was overall survival, tested hierarchically in prespecified populations—ie, IC2/3, followed by IC1/2/3, followed by the intention-to-treat population. A total of 234 patients (116 in the atezolizumab group, 118 in the chemotherapy group) were in the IC2/3 population.

In the intention-to-treat population, grade 3 or 4 treatment-related adverse events occurred in 20% of the atezolizumab group vs 43% of the chemotherapy group; the most common in the atezolizumab group were fatigue, anemia, and asthenia (2% each), and the most common in the chemotherapy group was neutropenia (11%). Adverse events led to discontinuation of treatment in 3% vs 14% of patients in the intent-to-treat population.

The investigators concluded, “Atezolizumab was not associated with significantly longer overall survival than chemotherapy in patients with platinum-refractory metastatic urothelial carcinoma overexpressing PD-L1 (IC2/3). However, the safety profile for atezolizumab was favourable compared with chemotherapy. Exploratory analysis of the intention-to-treat population showed well-tolerated, durable responses in line with previous phase II data for atezolizumab in this setting.”